The primary goal of this COBRE proposal is to increase the number of NIH-supported biomedical researchers in the state of South Carolina, particularly at Clemson University (CU). For this purpose, CU's unique strengths in biomaterials and tissue engineering will be complemented by expertise in medicine and developmental biology at the Medical University of South Carolina (MUSC) and the University of South Carolina (USC) to establish a Center of Biomaterials for Tissue Regeneration (CBTR) at CU. To accomplish the center's goal, an outstanding cadre of mentors will mentor junior investigators toward independence as NIH-supported investigators. The center's tissue-regeneration theme simultaneously fits South Carolina's strength in regenerative medicine while addressing a significant cause of mortality and morbidity worldwide: End-stage organ failure and tissue loss create healthcare costs of nearly $400 billion annually in the US alone. Research in tissue regeneration offers the possibility of relief for these human and economic costs through restoration of functional tissues. The scientific focus of this center will be regulation of tissue regeneration through cell biomaterials interactions. Four projects from junior investigators have been rigorously selected to fit this theme. These projects are 1) Stem cell-myocyte electrical coupling via a laser-patterned cell bridge;2) Biomaterials for guided neural regeneration;3) BMP-4 as a novel angiogenic factor and its potential use in tissue engineering;and 4) Endothelial response-guided design of hyaluronan-based vascular grafts. These target investigators will be paired with mentors who are established, NIH-supported researchers with excellent track records in mentoring and with surgeons who will keep projects clinically relevant. The projects will be supported by a well-organized infrastructure and three state-of-the-art core facilities (Materials Synthesis, Characterization and Testing, Histology and Imaging, and Cell and Molecular Engineering). We have unprecedented state and institutional support to establish this center. CU will recruit three junior investigators to expand activities of this center. The state of South Carolina has also approved $2M at each institution (CU, MUSC, and USC) to support endowed chairs in regenerative medicine;the endowments have been matched by each institution to yield a total of $12M. Our nationally recognized External Advisory Committee members will critically evaluate the center's progress. This COBRE will significantly augment collaborative efforts in South Carolina to recruit, train, and retain a critical mass of investigators with cross-disciplinary skills to collaborate effectively in the research area of regenerative medicine.